Functional Asplenism

Introduction

The spleen is the largest lymphoid organ and has a crucial function in the immune system. The spleen is responsible for the production and maturation of IgM, B lymphocytes, and opsonins. The spleen most importantly protects against infections from polysaccharide-encapsulated bacteria including Streptococcus pneumoniae, Haemophilus influenzae type B, Neisseria meningitidis, Escherichia coli, Salmonella, Klebsiella, and group B Streptococci (SHiNE SKiS). The spleen also acts as the primary reservoir for platelets and as a filter for red blood cells (RBCs), removing damaged or malformed RBCs from the circulation. In addition, the spleen performs extramedullary hematopoiesis.

Etiology

Functional asplenism is characterized by the loss of phagocytic activity while retaining splenic tissue. Functional asplenism is a condition that has been described in a large number of diseases including many autoimmune diseases, celiac disease, inflammatory bowel disease, sickle cell disease, beta thalassemia, chronic graft-versus-host disease, nephrotic syndrome and advanced HIV infection.

Epidemiology

The prevalence and incidence of functional asplenism are dependent on the prevalence and incidence of the precipitating diseases.

Pathophysiology

Functional asplenism is a gradual process that begins with hyposplenism. The process is not well understood. With diseases like sickle cell, researchers believe that entrapment of red blood cells (RBCs) in the spleen followed by splenic infarction leads to hyposplenism. The hyposplenism eventually proceeds to functional asplenism by autosplenectomy. In other hematologic disorders, functional asplenism occurs due to splenic tissue infiltration by a number of mechanisms including infiltration of tumor cells, sarcoid, amyloid deposition or even by a vascular occlusion.

History and Physical

Patients will usually present with history of an underlying disease that causes functional asplenism. There are no specific physical signs that suggests asplenism.

Evaluation

The peripheral blood smear is key to the evaluation for functional asplenism. The presence of Howell-Jolly bodies on a peripheral blood smear is indicative of abnormal spleen function. Howell-Jolly bodies are nuclear remnants of old RBCs that are typically removed by the spleen. Although they are typically found on peripheral blood smear, a flow cytometry-based assay for Howell-Jolly bodies is currently under investigation. Acanthocytes, large cells, Heinz bodies, and iron granules may also be observed on a peripheral blood smear. Demonstration of many of these abnormalities requires special dyes and microscopy. The presence and quantitation of “pitted” RBCs have been used to determine the function of remaining splenic tissue. Thrombocytosis, lymphocytosis, and monocytosis are additional hematological signs of functional asplenism. A 99Tc-labelled radiocolloid scan is helpful in the evaluation of splenic function by measuring the uptake of injected radio-labeled particles by the splenic endothelium relative to the liver. This scan provides information regarding the phagocytic function of the spleen. Liver-Spleen scintigraphy has the disadvantage of being invasive and time-consuming for patients. Newer methods that are currently in use include immune response upon vaccination or the evaluation of the functionality of specific B-cell subsets. Functional asplenia is also associated with small, avascular spleens on Doppler sonography.

Treatment / Management

Vaccines and prophylactic antibiotics are used as preventive measures against serious complications. Antibiotic prophylaxis is not routinely suggested for all patients with FH, and local microorganism resistance should be taken into consideration. However, it is suggested that patients be on lifelong penicillin V 500 mg twice daily or amoxicillin 500 mg once daily. Erythromycin 250 mg twice a day should be used in penicillin-allergic patients. Antimalarials should be given to patients traveling to malaria-endemic areas. Asplenic patients should also receive the pneumococcal vaccine, the H. influenza type-B conjugate vaccine as well as the meningococcal C-conjugate vaccine. Annual influenza immunization should also be provided.

Studies have shown a significant reduction in the percentage of serious infection in patients after immunization with pneumococcal vaccines. The commonly used pneumococcal polysaccharide vaccine requires the presence of IgM memory B cells and is therefore ineffective in asplenic subjects. In functionally asplenic patients, the pneumococcal conjugate vaccine is more effective, because it employs a T-cell-dependent mechanism, and should be the preferred vaccine in these situations. Vaccines are thought to be better when the spleen is intact. Hence, the vaccine should be given 2 weeks prior to surgery in patients undergoing splenectomy.

Complications

Overwhelming Post-Splenectomy Infection (OPSI)

OPSI is a syndrome that is encountered in post-splenectomy, hyposplenic and functional asplenic patients. Bacteremia caused by encapsulated microorganisms characterize the syndrome. The syndrome might present without a visible primary source of infection, and with a short prodromal phase, Clinical presentations include septic shock, disseminated intravascular coagulopathy, and bilateral adrenal hemorrhage. OPSI is a medical emergency and administration of antibiotics should be administered promptly along with supportive measures. Hyposplenic patients might already be on prophylactic antibiotics, and hence, cultures might be negative; however, antibiotic therapy should continue. Empiric parental antibiotic therapy should include vancomycin and either cefotaxime or ceftriaxone. Although the efficacy of intravenous immunoglobulin (IVIg) treatment for asplenic sepsis has not been proven, some experts recommend its administration in this situation. The morbidity of OPSI is high, and death may result in 24 to 48 hours, with mortality rates of 50% to 70%. This syndrome has been observed up to 10 to 30 years post-diagnosis with hyposplenism. Some series indicate that the risk of OPSI decreases with the time elapsed since splenectomy, while other studies do not show a significant reduction. The most commonly reported pathogen in OPSI is Streptococcus pneumoniae.

Thrombocytosis

Functional asplenism is almost always associated with secondary elevation of platelet count because the spleen is the main site of platelets’ destruction. However, this is not seen in patients with liver cirrhosis and portal hypertension. These patients present with thrombocytopenia rather than thrombocytosis due to impaired liver function. Thrombocytosis increases the risk of thrombotic events. Venous thrombosis in patients with asplenism is associated with platelet counts greater than 600 to 800 k/microliter and occurs in approximately 5% of patients. Thrombocytosis can also cause arterial thrombosis leading to myocardial infarction and cerebrovascular accidents. Some patients are advised by their doctors to take aspirin or even a cytoreductive agent such as hydroxyurea or anagrelide to reduce the risk of thrombotic events.

Pearls and Other Issues

Knowledge of the crucial and protective functions of the spleen show the importance of recognizing functional asplenism, a condition most commonly seen in patients with autoimmune diseases and a variety of hematological disorders. OPSI, as well as thrombotic events, are serious medical emergencies that require prompt intervention. OPSI morbidity may be limited with prompt recognition of the high-risk nature of illness in asplenic patients. The simple interventions of immunizations and prophylactic antibiotics are expected to reduce the frequency of OPSI and decrease its mortality despite the controversy over antibiotic use in asplenic patients.